BMS-182123, a fungal metabolite that inhibits the production of TNF- alpha by macrophages and monocytes

  • Warr G
  • Veitch J
  • Walsh A
 et al. 
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Abstract

A fungal metabolite, BMS-182123, which inhibited bacterial endotoxin- induced production of tumor necrosis factor (TNF-alpha) in murine macrophages and human peripheral blood monocytes (in vitro), was isolated from the culture broth of Penicillium chrysogenum strain V39673. The effective BMS-182123 concentration (IC50) resulting in 50% inhibition of lipopolysaccharide-induced TNF-alpha production in murine macrophages and human monocytes was 600 ng/ml and 4.0 microgram/ml, respectively. BMS-182123 suppressed the lipopolysaccharide-induced TNF- alpha promoter activity and did not affect the stability of posttranscriptional mRNA. Addition of hydrophobic resin, Amberlite XAD- 8 (1%), to the fermentation enhanced the production of BMS-182123 by 5.5 fold. A total of 577 mg pure BMS-182123 was recovered from a 250- liter fermentation supplemented with 1% Amberlite XAD-8

Author-supplied keywords

  • Affect
  • Animal
  • Base Sequence
  • Bridged Compounds
  • Connecticut
  • Culture
  • DNA Probes
  • Dna
  • Fermentation
  • Human
  • In Vitro
  • Japan
  • Lipopolysaccharides
  • Macrophages
  • Messenger
  • Mice
  • Molecular Sequence Data
  • Molecular Structure
  • Monocytes
  • Necrosis
  • Penicillium
  • Penicillium chrysogenum
  • Promoter Regions (Genetics)
  • RNA
  • Research
  • Rna
  • TNF alpha
  • Tumor Necrosis Factor/SBIR Grant/Thrombo
  • antagonists & inhibitors
  • bacterial
  • biosynthesis
  • blood
  • chemistry
  • classification
  • drug effects
  • factor
  • genetics
  • metabolism
  • murine
  • pharmacology
  • probe

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Authors

  • Glenn A Warr

  • Judith A Veitch

  • Ann W Walsh

  • Grace A Hesler

  • Dolores M Pirnik

  • John E Leet

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